Abstract PS3-02-30 : Ancestry-specific prevalence of pathogenic variants among patients with breast cancer who do not meet guidelines for genetic testing

Abstract Background Patients with breast cancer (BC) who harbor germline pathogenic variants (PVs) in hereditary cancer genes have improved survival when their surgical and treatment decisions are tailored to their specific genetic alterations. Additionally, the identification of germline PVs is crucial for family members, as it allows for interventions that can decrease cancer-related morbidity and mortality. Commonly utilized guidelines recommend genetic testing only under specific conditions: if cancer is diagnosed at a young age, typically at or before the age of 50; if there is a strong family history (FH) of cancer; or if there are specific tumor characteristics. Several studies have demonstrated that many patients who do not meet these criteria unknowingly carry PVs and may, therefore, be receiving suboptimal care. In the United States, Black and Hispanic women face disproportionately high rates of BC mortality, highlighting the importance of genetic testing in these populations. It is unclear whether guideline-based restrictions differentially impact women of certain ancestral backgrounds. Here, we explore this question by estimating PV prevalence among BC patients of Asian, Black/African, Hispanic, Multiple, and White/non-Hispanic ancestries who do not meet guidelines for genetic testing. Methods Multivariable logistic regression models were constructed to analyze trends in the prevalence of PVs based on age, personal/family history, and ancestry in a consecutive cohort of patients referred for hereditary cancer testing with a multigene panel. We report ancestry-specific model-based estimates of prevalence for patients diagnosed with BC at older ages with no FH and no prior personal history of cancer of any type. Prevalence is summarized overall for 25-48 hereditary cancer genes with guideline-based medical management recommendations, as well as for the genes most frequently implicated in BC. Results The study cohort comprised 245,669 female patients affected by BC. There were 8,025 (3.3%) Asian, 25,900 (10.5%) Black/African, 20,022 (8.1%) Hispanic, 141,279 (57.5%) White/non-Hispanic patients, and 16,689 (6.8%) patients with multiple self-reported ancestries. Estimates of PV prevalence for a patient with BC with no FH and no prior personal history of cancer of any type were similar across ancestries, with the highest prevalence among Hispanic women (Table). Overall prevalence estimates were 6.3% for those diagnosed at age 50 and 3.6% among those diagnosed at age 80. PVs were most frequently identified in BRCA1, BRCA2, CHEK2, ATM, and PALB2 (Table). Conclusions Among patients with BC of all ancestries, a substantial fraction of patients who do not meet guidelines for genetic testing may unknowingly carry PVs. Elimination of age-based restrictions on genetic testing could improve the survival of patients with BC and positively impact their family members. Citation Format: R. Bernhisel, M. Kucera, S. Cummings, E. Smith, T. Simmons, E. Hughes. Ancestry-specific prevalence of pathogenic variants among patients with breast cancer who do not meet guidelines for genetic testing abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-30.